The Papanicolaou (Pap) test is a widely-used method of cervical screening that detects abnormalities in cervical and endometrial cells, including pre-cancerous and cancerous lesions. The Pap test is widely used because it is simple, minimally invasive, and inexpensive. The test generally involves taking a sample of cells from the cervix using a collection device, and assaying the cells for certain diagnostic characteristics that are indicative of the presence of Human Papillomaviruses (HPV). Early detection of cervical abnormalities is essential for effective treatment, and regular Pap screening has reduced the number of annual deaths in the United States by more than 60% since its introduction in 1955 (National Cancer Institute).
To obtain a cervical sample, clinicians generally use a brush or a spatula to collect cells from the cervix and the endocervical canal. The specimen is then either directly smeared onto a glass slide (i.e., conventional “Pap smear”), or collected into a liquid based cytology medium (LBC). With LBC, the collection device is submerged in a preservative medium such as THINPREP® PRESERVCYT® Solution available from Hologic, Inc. (Bedford, Mass.) and stirred to release cells into the medium. Exposure to the LBC medium fixes the cells, enabling them to be evaluated for cell morphology. Greater details of useful LBC mediums can be found in U.S. Pat. No. 6,531,317 which is incorporated herein by reference in its entirety.
The current standard of care is to fix a portion of the collected cells on a slide for evaluation of cell morphology. The slides may be prepared by hand (“Pap smear”), however superior results can be obtained with automated systems, such as Hologic's THINPREP® Pap test combined with the THINPREP® Imaging System. This methodology is superior to the conventional Pap smear because of improved accuracy and increased disease detection (citation—Surveillance, Epidemiology, and End Results (SEER) Program. SEER Database: Incidence-SEER 9 Regs Public-Use, November 2004 Sub (1973-2002), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2005, based on November 2004 submission). Once the cells are fixed, the sample may be screened for atypical squamous cells, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions, squamous cell carcinomas, atypical glandular cells, adenocarcinomas and other cytologic abnormalities. See, e.g., the Bethesda System for Reporting Cervical Cytology.
Recent advances in genetic screening technologies have made it possible to screen for genetic changes indicative of cancer or infection. For example, cervical samples may be collected and screened for molecular diagnostics using a genetic assay, such as hybrid assay, multiplex PCR, or direct sequencing. The sample may be screened against a database of genetic markers to identify a woman's risk of cervical cancer, by typing for HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, HPV-68, HPV-73 or HPV-82. The screening may be based upon DNA, RNA, or some combination thereof. Commercial systems for diagnostic screening for HPV are available from Hologic, Inc., e.g., CERVISTA® HPV or APTIMA® HPV assays.
While the standard of care for cervical screening in the United States is still the Pap test, the U.S. Food and Drug Administration recently cleared the way for genetic testing alone to be used to screen women for cervical cancer. However, groups such as the American Medical Women's Association have expressed concern that genetic testing alone without concurrent morphology screening will result in too many women receiving treatment when those women are merely carriers of HPV and don't have any immediate risk of developing cervical cancer. See “FDA approves Roche Genetic Test as an Alternative to Pap Smear for Cervical Cancer Screening,” Associated Press, Apr. 24, 2014, incorporated by reference herein in its entirety.